PROJECT SUMMARY In Ugandan fisherfolk communities, HIV prevalence is an order of magnitude higher than in the Ugandan general population, and high HIV prevalence among fisherfolk helps to drive the general epidemic. In a prior R21 study, we demonstrated that bringing HIV testing to fisherfolk communities, where healthcare facilities are scarce, can identify a large number of high-risk HIV-negative fisherfolk. To have a significant impact on the HIV epidemic among fisherfolk, a key next step in this research program would be to offer pre-exposure prophylaxis (PrEP; a highly effective and safe daily pill containing tenofovir and emtricitabine to prevent HIV) to high-risk HIV-negative fisherfolk following HIV testing. Although the 2016 Ugandan HIV prevention and treatment guidelines recommend PrEP for HIV prevention in fisherfolk, there is currently no governmental support for PrEP implementation in fisherfolk communities. Pilot data are urgently needed to demonstrate to the Ugandan Ministry of Health that PrEP can be feasibly delivered to fisherfolk, in order to secure government support for PrEP for fisherfolk. The Specific Aims are: (1) To conduct formative qualitative research to examine barriers to and facilitators of PrEP uptake, and to obtain input on acceptable PrEP messaging and provision, for fisherfolk communities on Lake Victoria, Uganda; and (2) To conduct a mixed-methods analysis comparing the implementation of community-based vs. healthcare facility-based PrEP provision for fisherfolk communities on Lake Victoria, Uganda. For both PrEP interventions, we will conduct monthly HIV testing and PrEP and antiretroviral treatment provision events, using messages developed from the formative work to raise awareness about PrEP. PrEP will be offered to 100 fisherfolk in two Lake Victoria landing sites during testing events on specified days of the month: In one site, PrEP will be distributed in a nearby healthcare facility during monthly events, and in the other site, PrEP will be distributed in a temporary community space. Among those who are non-adherent (based on refill data), PrEP provision will be supplemented via PrEP delivery by community health workers or at community PrEP pick-up points, based on strategies elicited in the formative work. To evaluate implementation, we will conduct semi-structured interviews with healthcare providers and fisherfolk who do and do not decide to initiate PrEP, and obtain medical records data to compare the proportion of fisherfolk: identified as PrEP-eligible, who initiate PrEP, who adhere to PrEP (i.e., refills over 6 mos.), who seroconvert, and who discontinue PrEP, overall and by socio-demographic characteristics (e.g., gender). We will engage with Ugandan Ministry of Health policymakers throughout the research, to keep them apprised of results and to determine directions for future policy around PrEP for fisherfolk. To realize the 90- 90-90 goals, it is critical to seek out the hardest to reach, most at-risk populations such as fisherfolk, who reside and work in areas without easy access to healthcare.